Janus kinase (JAK) is a family of intracellular non-receptor tyrosine kinases for cytokine receptor signaling in blood formation and immune responses, which is comprised of Janus kinase 1 (JAK1), Janus kinase 2 (JAK2), Janus kinase 3 (JAK3), and tyrosin kinase 2 (TYK2) (Yamaoka et al., Genome Biol. 2004, 5, 253). The JAK kinases are implicated in myeloproliferative disorders, cancers, including blood borne and solid tumors, and immunodeficiency (Vainchenker et al., Sem. Cell Dev. Biol. 2008, 19, 385-393). Exemplary disorders include chronic myeloid leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF), chronic eosinophilic leukemia (CEL), chronic myelomonocytic leukemia (CMML), and systemic mastocytosis (SM). Myeloproliferative disorders are believed to arise from either gain-of-function mutations to JAK itself or from activation by the oncoprotein BCR-ABL, which specifically activates the JAK2 pathway. For example, mutations and translocations in the JAK genes leading to constitutively active JAK proteins are associated with a variety of hematopoietic malignancies, including the myeloproliferative disorders (JAK2), acute lymphoblastic leukemia (JAK2), acute myeloid leukemia (JAK2, JAK1), acute megakaryoblastic leukemia (JAK2, JAK3) and T-cell precursor acute lymphoblastic leukemia (JAK1) (Vainchenker et al., Sem. Cell Dev. Biol. 2008, 19, 385-393). In contrast, loss-of-function mutations of JAK3 and TYK2 lead to immunodeficiency (Vainchenker et al., Sem. Cell Dev. Biol. 2008, 19, 385-393). Therefore, there is a need for JAK inhibitors as therapeutic agents for treating JAK-mediated disorders or diseases.